From infancy to adulthood, those affected could show symptoms at any age. The progression of symptoms over time is different for every person with NPC. This unpredictability could be due to the type of faulty gene inherited, environmental factors, and/or the individual's unique DNA.

NPC is one of 100+ diseases that cause Childhood Dementia affecting the ability to think, reason, and remember compared to other people of the same age⁵.

Other disease symptoms are⁴:

• Jaundice at (or shortly after) birth

• Enlarged spleen and/or liver (hepatosplenamegaly)

• Difficulty with upward and downward eye movements (Vertical Supranuclear Gaze Palsy)

• Difficulty in posturing of limbs (dystonia)

• Unsteadiness of gait, clumsiness, problems in walking (ataxia)

• Slurred, irregular speech (dysarthria)

• Tremors accompanying movement

• Seizures

• Learning difficulties and progressive intellectual decline (Cognitive dysfunction – “dementia”)

• Psychological problems

• Sudden loss of muscle tone which may lead to falls (cataplexy)

• Loss of the ability to speak

• Loss of the ability to move facial muscles or swallow, making feeding through a stomach tube necessary

The final symptom in most cases, is aspiration from pneumonia due to losing the ability to swallow.

The rate at which the disease progresses vary greatly between patients. The average life expectancy is 13 years old, however, some patients have lived into their late adulthood with reported ages ranging from 0 to 69 years old⁷.

Children who develop neurological symptoms in early childhood are thought to have a more aggressive form of the disease, whilst others may remain symptom-free for many years.

Diagnoses is usually conducted clinically and confirmed genetically. It can involve several of the following steps.

1. Biomarker Profiling: Doctors look for increased levels of oxidized cholesterol products (oxysterols) and lyso-sphingolipids in blood plasma, as well as bile acids in blood plasma and urine⁸.

2. Genetic Testing: This involves checking for changes in the NPC1 or NPC2 genes, which are responsible for the disease⁸.

3. Fibroblast Assay: A small skin biopsy is taken to grow fibroblasts, which are then tested for cholesterol esterification and stained for unesterified cholesterol using filipin¹.

   
   

These methods help ensure an accurate diagnosis, although the process can be complex due to the variability of symptoms.

NPD conditions are caused by specific DNA changes that disrupts our body’s natural ability to get rid of toxic materials. These conditions are called lysosomal storage disorders as they impact the cell’s ability to break down fats in the lysosome (the cell’s recycling and sorting centre). This build-up causes large-scale cell death across the body and leads to the development of disease symptoms in multiple organs³.

Niemann-Pick Disease Type C (NPC) is inherited in an autosomal recessive manner.

A carrier is a person who has one copy of the faulty gene. When a child is affected by NPC, they must inherit two copies of the faulty gene (one from each parent).

When both parents are carriers of the NPC1 or NPC2 gene changes, there is a 25% chance with each pregnancy that their child will have NPC, a 50% chance that the child will be a carrier like the parents, and a 25% chance that the child will not inherit the change at all ⁹¹⁰.

Carrier parents typically do not show symptoms of the disease, which can make it challenging to identify the risk without genetic testing. Genetic counseling is often recommended for families with a history of NPC to understand their risks and the implications for future pregnancies⁹¹⁰.

Treatment of NPD conditions is complex and often requires a multi-disciplinary approach with a range of specialists to help manage symptoms.

Visit Treatments for more information.